Application of mesoporous silica for the oral delivery of poorly water-soluble drugs
| dc.check.embargoformat | Both hard copy thesis and e-thesis | en |
| dc.check.entireThesis | Entire Thesis Restricted | |
| dc.check.opt-out | Not applicable | en |
| dc.check.reason | This thesis is due for publication or the author is actively seeking to publish this material | en |
| dc.contributor.advisor | Crean, Abina M. | en |
| dc.contributor.advisor | Ryan, Katie B. | en |
| dc.contributor.author | Ahern, Robert J. | |
| dc.contributor.funder | Science Foundation Ireland | en |
| dc.date.accessioned | 2014-02-12T15:04:06Z | |
| dc.date.issued | 2014 | |
| dc.date.submitted | 2014 | |
| dc.description.abstract | The objective of this thesis was to improve the dissolution rate of the poorly waters-soluble drug, fenofibrate by processing it with a high surface area carrier, mesoporous silica. The subsequent properties of the drug – silica composite were studied in terms of drug distribution within the silica matrix, solid state and release properties. Prior to commencing any experimental work, the properties of unprocessed mesoporous silica and fenofibrate were characterised (chapter 3), this allowed for comparison with the processed samples studied in later chapters. Fenofibrate was a highly stable, crystalline drug that did not adsorb moisture, even under long term accelerated storage conditions. It maintained its crystallinity even after SC-CO2 processing. Its dissolution rate was limited and dependent on the characteristics of the particular in vitro media studied. Mesoporous silica had a large surface area and mesopore volume and readily picked up moisture when stored under long term accelerated storage conditions (75% RH, 40 oC). It maintained its mesopore character after SC-CO2 processing. A variety of methods were employed to process fenofibrate with mesoporous silica including physical mixing, melt method, solvent impregnation and novel methods such as liquid and supercritical carbon dioxide (SC-CO2) (chapter 4). It was found that it was important to break down the fenofibrate particulate structure to a molecular state to enable drug molecules enter into the silica mesopores. While all processing methods led to some increase in fenofibrate release properties; the impregnation, liquid and SC-CO2 methods produced the most rapid release rates. SC-CO2 processing was further studied with a view to optimising the processing parameters to achieve the highest drug-loading efficiency possible (chapter 5). In this thesis, it was that SC-CO2 processing pressure had a bearing on drug-loading efficiency. Neither pressure, duration or depressurisation rate affected drug solid state or release properties. The amount of drug that could be loaded onto to the mesoporous silica successfully was also investigated at different ratios of drug mass to silica surface area under constant SC-CO2 conditions; as the drug – silica ratio increased, the drug-loading efficiency decreased, while there was no effect on drug solid state or release properties. The influence of the number of drug-loading steps was investigated (chapter 6) with a view to increasing the drug-loading efficiency. This multiple step approach did not yield an increase in drug-loading efficiency compared to the single step approach. It was also an objective in this chapter to understand how much drug could be loaded into silica mesopores; a method based on the known volume of the mesopores and true density of drug was investigated. However, this approach led to serious repercussions in terms of the subsequent solid state nature of the drug and its release performance; there was significant drug crystallinity and reduced release extent. The impact of in vitro release media on fenofibrate release was also studied (chapter 6). Here it was seen that media containing HCl led to reduced drug release over time compared to equivalent media not containing HCl. The key findings of this thesis are discussed in chapter 7 and included: 1. Drug – silica processing method strongly influenced drug distribution within the silica matrix, drug solid state and release. 2. The silica surface area and mesopore volume also influenced how much drug could be loaded. It was shown that SC-CO2 processing variables such as processing pressure (13.79 – 41.37 MPa), duration time (4 – 24 h) and depressurisation rate (rapid or controlled) did not influence the drug distribution within the SBA- 15 matrix, drug solid state form or release. Possible avenues of research to be considered going forward include the development and application of high resolution imaging techniques to visualise drug molecules within the silica mesopores. Also, the issues surrounding SBA-15 usage in a pharmaceutical manufacturing environment should be addressed. | en |
| dc.description.sponsorship | Science Foundation Ireland (Solid State Pharmaceutical Cluster 07/SRC/B1158) | en |
| dc.description.status | Not peer reviewed | en |
| dc.description.version | Accepted Version | |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.citation | Ahern, R. J. 2014. Application of mesoporous silica for the oral delivery of poorly water-soluble drugs. PhD Thesis, University College Cork. | en |
| dc.identifier.endpage | 296 | |
| dc.identifier.uri | https://hdl.handle.net/10468/1381 | |
| dc.language.iso | en | en |
| dc.publisher | University College Cork | en |
| dc.rights | © 2014, Robert J. Ahern | en |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | en |
| dc.subject | Supercritical carbon dioxide | en |
| dc.subject | SBA-15 | en |
| dc.subject | Mesoporous silica | en |
| dc.subject | Fenofibrate | en |
| dc.subject | Solid state | en |
| dc.subject | Amorphous | en |
| dc.subject | Drug dissolution enhancement | en |
| dc.subject | High surface area | en |
| dc.subject | Drug-loading | en |
| dc.subject | Poorly water-soluble | en |
| dc.subject.lcsh | Drugs Solubility | en |
| dc.subject.lcsh | Mesoporous materials | en |
| dc.thesis.opt-out | false | |
| dc.title | Application of mesoporous silica for the oral delivery of poorly water-soluble drugs | en |
| dc.type | Doctoral thesis | en |
| dc.type.qualificationlevel | Doctoral | en |
| dc.type.qualificationname | PhD (Medicine and Health) | en |
| ucc.workflow.supervisor | a.crean@ucc.ie |
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